Effect of pisiferic acid and its derivatives on cytotoxicity macromolecular synthesis and dna polymerase α of hela cells

Abstract

1. 1. Seventy-seven derivatives of pisiferic acid (2), an antimicrobial diterpenoid, were tested for cytotoxicity against HeLa cells and 9 derivatives were found to show cytotoxicity at < 2 μg/ml dose (IC 50). 2. 2. Hydrophobicity was revealed to be an important factor for cytotoxicity of the derivatives. 3. 3. Compound 2 inhibited predominantly DNA synthesis in HeLa cells as compared with RNA and protein synthesis. 4. 4. No direct interaction between 2 and nucleic acid bases was indicated by a u.v. spectral method. 5. 5. Several of the pisiferie acid species showed inhibitory action on HeLa DNA polymerase α, and the inhibitory activity was about 1 20 of aphidicolin.